The invention relates to monitoring oral administration of pharmaceuticals in animals and humans, e.g., monitoring self-administration of pharmaceuticals in human patients.
A major problem in optimal drug administration is patient compliance. In clinical trials of new drugs, and in normal treatment regimens with approved drugs, it is important to establish that patients are complying with prescribed treatment programs. In clinical trials, lack of compliance compromises the data developed in support of new drug development, and can result in discontinuation of development programs for potentially useful drugs. Conducting these human trialls carefully and accurately is crucial since these data will be relied on to save lives. In addition, conducting these trials efficiently is important because this step is a very expensive and time consuming part of bringing a drug from the discovery stage to the bedside.
For commercially available drugs, lack of compliance may cause a physician subsequently to over-prescribe a treatment or switch to another, possibly less effective, treatment. In addition, lack of compliance in patients with communicable diseases can threaten the public health. For example, tuberculosis is on the rise at least in part because many patients fail to complete an established effective treatment course. Patients will skip doses, take them at the wrong time intervals, or take multiple doses at a time, especially when they are about to visit their physician. Society, to avoid a public health disaster, is forced to send nurses door to door simply to ensure that patients have actually swallowed their pills. Ideally, such precious medical resources would be better utilized as more than just "pill police."
In other cases, where drug and alcohol abusers are placed on specific treatment regimens, it is critical that the medication is taken faithfully. To that end, methadone patients are required to come to a clinic daily to ensure that the treatment is administered. The availability of better methods for compliance monitoring would provide physicians with a tool that would allow them to give patients greater responsibility in administering their own treatment, reducing health care costs and improving the quality of life of the patient. In the case of methadone, a means for differentiating legal methadone from illegal opiates would be very useful.
Ideally, compliance with treatment regimens includes both taking the proper amount of medication (no more, no less) and taking it at the correct time intervals (evenly spaced). This assures that levels of the medication in the bloodstream will remain consistent, allowing the drug to perform optimally.
Assay methods are sometimes used to monitor patients for compliance to assure that they are taking medication as prescribed. Assay methods that would detect a patient-ingested marker over a period of time longer than 24 hours would be particularly useful for physicians and healthcare workers when they see their patients at widely spaced intervals. Presently, no such methods exist.
One report in the literature of the use of a labelling compound to monitor therapeutic regimen compliance is Publication RV31899 (1995) from duPont de Nemours Co., manufacturers of the drug Naltrexone, used to treat alcohol dependence. The duPont product monograph states: "Subjects were prescribed 50 mg/d of REVIA.TM. [Naltrexone] or placebo Riboflavin, 25 mg was also incorporated into all capsules to evaluate patient compliance. Urine samples were inspected biweekly using a UV light to detect the presence of riboflavin. This is an example of a crude, qualitative method to determine the degree of patient compliance with Naltrexone treatment. Riboflavin concentrations of 1.5 .mu.g/ml or greater were considered positive, as less than 1.5 .mu.g/ml of urinary riboflavin is typically observed with a normal diet.
Another concern arises in the testing of athletes, employees, and patients for drug abuse, where questions can arise whether urine samples have been switched or altered (diluted).
Finally, it is often important in animal husbandry to ensure that livestock have consumed certain foods or veterinary products, from concern both for the health of the animal, and for the wholesomeness and safety of the food products derived from the animal.